How do you minimize risk, which although is low can be serious? Is there a change in the urinary environment which increases the possibility of UTI or genital infection? If so, is that related to the amount of sugar excreted and therefore the importance of diet in avoiding such risk? If not, what is the mechanism and what, if anything can be done to minimize the risk associated with canagliflozin? And since a known rapamycin risk is the possibility of bacterial infection, are we setting up a higher risk situation by taking rapa and canagliflozin together?
2 Likes
These are all really good questions, and I think we do need to try to get answers to them.
I may be wrong, but my thinking is that the UTI risk is higher for females, so I’ve been less concerned about that (as a male).
I also take a lower dose (10mg of empagliflozin) - and do it in a pulsed dosing - approx. 3 weeks on, 1 week off. Not that there is any research to support this approach.
I also have Azithromycin on hand if I get any bacterial infections - so can immediately start taking it if I do have any problems.
2 Likes
I just priced Canagliflozin at Alldaychemist. $2.20 per 100 mg tablet. They are reliable, but that is quite a bit higher than what I was expecting. Are there any other proven reliable India pharmacies?
@RapAdmin What do you think about taking Canagliflozin PRN, on days when the diet is planned to be less than optimal? Do you see it working quickly enough to matter on your CGM? I use enough carb restriction to not need it on most days, but then there are days when I know I’m not going to be good. Acarbose PRN has led to some awful gastric upset, so I’m not using it any longer.
2 Likes
Here is my experience with canagliflozin:
Canagliflozin for Anti-aging - One Month and 4 Month Updates
I’ve been taking 10mg empagliflozin for the past two months and its been going well. It has a big impact on flattening gluocose spikes, which seems to be a good thing for anti-aging (in males). I generally try to avoid processed foods and simple carbs - but do eat a lot of salads which can sometimes have a higher carb load, or some fruit like apples, which I like.
I also dose acarbose occasionally with meals when I haven’t taken empagliflozin or later in the day if I’ve taken empagliflozin earlier in the morning - but have the same issue as you with acarbose - a lot of gas most of the time, so its far from optimal.
5 Likes
Yes… $600 per month vs $60 a month from India.
I’ve been taking it on an as needed basis too. This is because I’ve read reports of fatigue and because SGLT2i selectively reduce levels of blood glucose only when it is high.
So at least as far as the CGM related benefits go, I don’t see a need unless there’s a high carb meal.
I however don’t know about other benefits or disadvantages. I’ve imagined that the cardioprotective and renal-protective properties of SGLT2i are downstream from lowering the blood glucose. But I might be wrong.
2 Likes
Dr Brad Stanfield believes SGLT2 inhibitors will be first longevity drugs prescribed by clinicians.
Despite his views on supplements, Stanfield believes that there are systems in place to allow longevity interventions to end up in clinical use, especially the Interventions Testing Program run by the US National Institute on Aging. He cites results seen in SGLT2 inhibitor Canagliflozin as an example.
“The Interventions Testing Program reported a median 14% lifespan extension in male mice with this medication,” says Stanfield. “That’s very interesting, but needs more work, and that work is being done in the clinical field.”
SGLT2 inhibitors are already being used to treat Type 2 diabetes, but Stanfield says clinical work is now indicating that these medications could also have an impact in heart failure, chronic kidney disease and weight loss.
“In terms of a so-called longevity medication, I think that SGLT2 inhibitors will be the first ones that will be prescribed and made widely available. That’s because they appear to provide significant protective effects for the kidneys. Our kidney function starts to decline from around the age of 30, so if we can use SGLT2 inhibitors to slow down or prevent that decline, that would be a powerful intervention. Of course, we’re waiting on the human data to come through, but there is a robust way of these things getting through to people.”
Read the full story:
6 Likes
A new SGLT2 inhibitor paper (open access):
Sodium-glucose-cotransporter 2 inhibitors (SGLT2is) demonstrate large cardiovascular benefit in both diabetic and non-diabetic, acute and chronic heart failure patients. These inhibitors have on-target (SGLT2 inhibition in the kidney) and off-target effects that likely both contribute to the reported cardiovascular benefit. Here we review the literature on direct effects of SGLT2is on various cardiac cells and derive at an unifying working hypothesis. SGLT2is acutely and directly (1) inhibit cardiac sodium transporters and alter ion homeostasis, (2) reduce inflammation and oxidative stress, (3) influence metabolism, and (4) improve cardiac function.
2 Likes
empagliflozin is way better - Cost-effectiveness of empagliflozin versus canagliflozin, dapagliflozin, or standard of care in patients with type 2 diabetes and established cardiovascular disease - PMC
2 Likes
Another new SGLT2i study with good results 
Full Paper:
5 Likes
Results: Compared with placebo, canagliflozin 100 mg reduced SBP by 3.43 mmHg and DBP by 1.05 mmHg. Canagliflozin 100 mg increased LDL-C by 0.10mmol/l and HDL cholesterol (HDL-C) by 0.05 mmol/l. Compared with placebo, canagliflozin 300 mg reduced SBP by 4.75 mmHg and DBP by 1.69 mmHg. Canagliflozin 300 mg increased LDL-C by 0.16 mmol/l and HDL-C by 0.06 mmol/l. Compared with canagliflozin 100 mg, canagliflozin 300 mg further reduced SBP by 1.21 mmHg and DBP by 0.64 mmHg, and further increased LDL-C by 0.06 mmol/l and HDL-C by 0.02 mmol/l. Compared with placebo and canagliflozin 100 mg, canagliflozin 300 mg increased the risk of UTI.
Conclusion: The current meta-analysis provides new evidence on different doses of canagliflozin as an antihypertensive agent in T2DM complicated by hypertension; however, LDL-C and the risk of UTI should be monitored.
1 Like
“Then they evaluated how treatment with the sodium glucose co-transporter 2 (SGLT2) inhibitor empagliflozin (Empa) improved blood vessel function and reduced arterial stiffness in aged male mice.”
1 Like
More new research:
SGLT-2i vs. Metformin:
Cardiovascular Outcomes in Patients Initiating First-Line Treatment of Type 2 Diabetes With Sodium–Glucose Cotransporter-2 Inhibitors Versus Metformin
Limitation:
Treatment selection was not randomized.
Conclusion:
As first-line T2D treatment, initiators receiving SGLT-2i showed a similar risk for MI/stroke/mortality, lower risk for HHF/mortality and HHF, and a similar safety profile except for an increased risk for genital infections compared with those receiving metformin.
2 Likes
Importantly, mean follow up was only 12 months. Since CVD development is a slow process, I’d only expect those relative risks of heart failure to further diverge (and maybe even see some lowered comparative risks for stroke/MI in the SGLT2i group?) as time goes on. Hopefully they’ll continue to follow these cohorts to see if that’s true.
I wonder what the relative rate of genital infections in men vs women was in the SGLT2i group?
Yes - I have also wondered about this… I’ve never heard of men getting UTIs, so I suspect its almost all women. But if someone knows differently, please post.
I think you’re taking SGLT2i for longevity, correct?
Have you had a chance to track say phenoage or any other longevity improvement marker? Liver or kidney function?
Its all been largely unchanged during time on Sglt2 inhibitors.